A cross-coupling reaction is an extremely important synthetic reaction which allows for direct formation of a bond between sp2 carbons or the like. In the cross-coupling reaction, an aryl halide or an alkenyl halide in which a halogen atom is connected to an sp2 carbon of aromatic series or olefin is reacted with an organo metallic compound or acetylene in the presence of a transition metal catalyst such as nickel and palladium. As the result, the halogen atom connected to the sp2 carbon of aromatic series or olefin is substituted by the organic group. Hence, the cross-coupling reaction is essential in constituting n-conjugated systems serving as key compounds of medicinal intermediates or molecular-scale electronics elements.
As the organometallic reagents used in the cross-coupling reaction, there are various kinds of organo metallic compounds, such as organo magnesium, zinc, boron, silicon, tin, or the like. Above all, currently, boron-based cross-coupling reagents in which boron is connected to sp2 carbon are most widely used due to its stability and excellent selectivity of cross-coupling reaction. Dozens of kinds of such boron-based cross-coupling reagents come onto the market from chemical producers such as TOKYO CHEMICAL INDUSTRY CO., LTD.
Further, also silicon-based cross-coupling reagents in which silicon is connected to sp2 carbon is greatly expected due to its selectivity of cross-coupling reaction, less toxicity, ease of preparation (see Non-Patent Document 1 (Armin de Meijere, François Diederich, Metal-Catalyzed Cross-Coupling Reactions, 2nd Edition, 2004 WILEY-VCH Verlag GmbH&Co.KGaA, Weinheim, p 163-216) or a similar document for example).
Of the silicon-based cross-coupling reagents, those in which all groups bound to silicon are organic groups are highly stable, but it is necessary to use an expensive fluoride ion as activators in using such silicon-based reagents to undergo the cross-coupling reaction. A method which requires no fluoride ions has been reported (see Non-Patent Document 2 (J. Org. Lett. 2002, 4, 3635-3638) and Non-Patent Document 3 (J. Org. Chem. 2004, 69, 8971-8974) or a similar document for example), but it is necessary to use a stoichiometric amount of transition metal promoters or strong bases.
Then, it has been reported that the cross-coupling reaction can be carried out without any fluoride ions by using: a silicon-based cross-coupling reagent in which organic groups on a silicon atom are partially substituted by halogens such as chlorine and fluorine atoms (see Patent Document 1 (Japanese Unexamined Patent Application No. 310972/1996 (Tokukaihei 8-310972) (Publication date: Nov. 26, 1996)) and Patent Document 2 (Japanese Unexamined Patent Application No. 283521/1992 (Tokukaihei 4-283521) (Publication date: Oct. 8, 1992)), Non-Patent Document 4 (Tetrahedron Lett. 1997, 38, 439-442), or a similar document for example); a silicon-based cross-coupling reagent in which organic groups on a silicon atom are partially substituted by alkoxyl groups (see Patent Document 2, Non-Patent Document 5 (Org. Lett. 2004, 6, 1147-1150), or a similar document for example); a silanol serving as a silicon-based cross-coupling reagent (see Non-Patent Document 6 (J. Org. Chem. 2000, 65, 5342-5349) or a similar document for example); and the like.
On the other hand, a cross-coupling reaction using intramolecular activation has also been reported (see Non-Patent Document 7 (J. Org. Chem. 2002, 67, 8450-8456), Non-Patent Document 8 (SYNLETT 2005, N0.1, pp 0176-0178), Non-Patent Document 9 (Chem. Pharm. Bull., 36(11)4622-4625 (1988)), and Non-Patent Document 10 (Organic Letters, 2004, Vol. 6, No. 23, 4379-4381) or a similar document for example). Non-Patent Document 7 discloses a method in which an intramolecularly-activated intermediate obtained by reacting (Z)-γ-trimethylsilylallyl alcohol with copper (I)t-butoxide cross-couples with an aryl halide in the presence of a palladium catalyst. Non-Patent Document 8 reports that a cross-coupling reaction of trialkylvinylsilane activated intramolecularly by a (Z)-β-carboxyl group is carried out in the presence of a palladium catalyst without any fluoride ions. Non-Patent Document 9 reports that triethylammonium bis(catecolate)alkenylsiliconates in which pentacoordinate silicon atoms react with allyl iodide to generate cross-coupling products. Non-Patent Document 10 reports that a cross-coupling reaction of pentacoordinate allyl bis(catechol)silicates and aryl bromide can be carried out by microwave irradiation.
Further, it is reported that, although not on the cross-coupling reaction, pentacoordinate silicates generated by an intramolecular reaction of o-silylbenzyl alcohol decompose under mild conditions and a silyl or benzyl group is transferred to undergo an addition reaction to carbonyl compounds (see Non-Patent Document 11 (Can. J. Chem. 78:1421-1427 (2000)) or a similar document for example).
The silicon-based cross-coupling reagent has excellent selectivity in the cross-coupling reaction as described above, and is complementary to the boron-based one since the silicon-based protocol is often applicable to a target compound which is not accessible by the boron-based one. However, the silicon-based cross-coupling reagent which has a highly stabile tetraorganosilicon structure and undergoes a cross-coupling reaction under mild conditions without fluoride activation has not been produced.
Non-Patent Documents 2 and 3 discloses a protocol allowing use of such the highly stable silicon-based cross-coupling reagent having all organic groups and the cross-coupling reaction without any fluoride ions. However, it is necessary to use a stoichiometric amount of transition metal promoters or strong bases. Further, each of Patent Documents 1 and 2 and Non-Patent Documents 4, 5, and 6 discloses that organosilicon compounds having electron-withdrawing hetero atoms such as halogen and oxygen atoms on a silicon atom participate in the cross-coupling reaction without using any fluoride ions. Nevertheless, they are not stable toward moisture, acid or alkali, and thus, not easy to handle.
In the protocols described in Non-Patent Documents 7 and 8 utilizing intramolecular activation, it is necessary that a hydroxyl group or a carboxyl group is introduced in an organic group which is transferred in the cross-coupling reaction. Therefore, the transferable organic group on the silicon atom is limited to such structures. Silicon-based cross-coupling reagent containing a pentacoordinate silicon atom, which is disclosed in Non-Patent Document 9, requires longer reaction time to complete the cross-coupling reaction, resulting in an insufficient yield. According to Non-Patent Document 10, it is necessary to irradiate a microwave, so that a device for irradiating the microwave is required and some troubles are caused in operating the device.
Non-Patent Document 11 describes that intramolecular activation is used merely to carry out an addition reaction to the carbonyl compound.
On the other hand, in the boron-based cross-coupling reagent used frequently for the cross-coupling reaction, a boron residue is difficult to recover and reuse, whereas there has been a strong need to develop a cross-coupling protocol which allows reuse of reagents in view of effective utilization of resources, reduction of environmental loading, and the like.
The present invention was made in view of the foregoing problems, and the object of the present invention is to provide (i) silicon-based cross-coupling reagents which have high stability and allow for the cross-coupling reaction under mild conditions without using any fluoride ions and (ii) a synthetic method of organic compounds using the organosilicon reagents.